Shp-2 regulates the TrkB receptor activity in the retinal ganglion cells under glaucomatous stress

Vivek K. Gupta*, Yuyi You, Alexander Klistorner, Stuart L. Graham

*Corresponding author for this work

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Tropomyosin-receptor-kinase B (TrkB receptor) activation plays an important role in the survival of retinal ganglion cells (RGCs). This study reports a novel finding that, SH2 domain. -containing phosphatase-2 (Shp-2) binds to the TrkB receptor in RGCs and negatively regulates its activity under glaucomatous stress. This enhanced binding of TrkB and Shp2 is mediated through caveolin. Caveolin 1 and 3 undergo hyper-phosphorylation in RGCs under stress and bind to the Shp2 phosphatase. Shp2 undergoes activation under glaucomatous stress conditions in RGCs in vivo with a concurrent loss of TrkB activity. Inhibiting the Shp2 phosphatase restored TrkB activity in cells exposed to excitotoxic and oxidative stress. Collectively, these findings implicate a molecular basis of Shp2 mediated TrkB deactivation leading to RGC degeneration observed in glaucoma.

Original languageEnglish
Pages (from-to)1643-1649
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1822
Issue number11
DOIs
Publication statusPublished - Nov 2012

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